Leicester Royal Infirmary

About: Leicester Royal Infirmary is a healthcare organization based out in Leicester, United Kingdom. It is known for research contribution in the topics: Population & Carotid endarterectomy. The organization has 5300 authors who have published 6204 publications receiving 208464 citations.

Localization of matrix metalloproteinase 2 within the aneurysmal and normal aortic wall

Abstract: Background Current research has shed new light on the role of matrix metalloproteinase (MMP) 2 in the development of abdominal aortic aneurysms (AAAs). MMP-2 is a major protease in the wall of small aneurysms and is produced at increased levels by smooth muscle cells derived from AAAs compared with normal controls. In vivo, MMP-2 is produced as an inactive proenzyme that is activated predominantly by the cell membrane-bound enzyme, membrane type 1 matrix metalloproteinase (MT1-MMP). This study investigated the production of the MMP-2–MT1-MMP–tissue inhibitor of metalloproteinases (TIMP) 2 system within the wall of aortic aneurysms and in age-matched control arterial tissue. Methods Arterial tissue from four patients with aortic aneurysms and four age-matched aortic samples was examined for the production and expression of MMP-2, TIMP-2 and MT1-MMP protein using immunohistochemistry, in situ hybridization and in situ zymography. Results All components of the MMP-2–TIMP-2–MT1-MMP enzyme system were detected in the arterial wall of both aneurysm and control samples, specifically in the medial tissue. The enzymes co-localized with medial smooth muscle cells. Gelatinolytic activity was localized to elastin fibres in normal and aneurysmal aorta. Conclusion The presence of MT1-MMP within the media of arterial tissue suggests a powerful pathway for the activation of MMP-2. The localization of the MMP-2–TIMP-2–MT1-MMP enzyme system to the medial layer of the arterial wall gives support to the concept that this system may play an aetiological role in the pathogenesis of AAAs. © 2000 British Journal of Surgery Society Ltd

Expression of the components and regulatory proteins of the alternative complement pathway and the membrane attack complex in normal and diseased synovium

Abstract: We have studied synthesis of the complement components and regulatory proteins of the alternative pathway and the membrane attack complex in synovial membrane. RNA was extracted from synovial tissue of patients with rheumatoid arthritis (RA) or osteoarthritis (OA) as well as from normal synovial membrane. Dot blot analysis showed the presence of mRNAs for all the complement components and regulatory proteins (C3, factor B, factor D, C5, C6, C7, C9, factor H, factor I, S-protein, SP-40, 40, DAF, MCP, CR1, CD59), except for properdin, C8α, C8β and C8γ in all three types of synovial membrane studied. In an attempt to determine which components were synthesised by each cell type, monocytes (mononuclear phagocytes), human umbilical vein endothelial cells (HUVEC), synovial membrane fibroblasts (from normal, OA and RA synovial membrane) and peripheral blood lymphocytes were cultured in vitro and secretion rates of individual components were measured and total cellular RNA analysed by northern blotting. Monocytes secreted properdin, C3, and factor H but not factor B, factor I, C5, C6, C7, C8 or C9. Fibroblasts and endothelial cells secreted factor B, factor H and factor I, but not properdin, C5, C6, C7, C8 or C9. Lymphocytes did not secrete any of these components. mRNAs encoding C3, factor B, factor H, S-protein, SP-40, 40, MCP and DAF were detected in all three other cell types (monocytes, fibroblasts and HUVEC), but factor I and CD59 mRNAs were not detected in monocytes. C5, C6, C7, C8α, C8β, CD8γ and C9 mRNAs were not detected in any of the cell types studied. Cell-specific differences were observed in the expression of the different mRNA species for DAF, MCP and CD59. The results of the present study demonstrate that synthesis of many complement components occurs in normal, RA and OA synovial membrane, and that this may be explained in part by synthesis in mononuclear phagocytes, endothelial cells and fibroblasts. The cellular sources of C5, C6, C7 and C9 mRNAs in synovial membrane have not been determined. The data also show that there are important cell-specific differences in the expression of the genes encoding both the alternative complement pathway components and the membrane regulatory components. These differences require further investigation.

Assessment of dynamic cerebral autoregulation based on spontaneous fluctuations in arterial blood pressure and intracranial pressure.

Abstract: Assessments of dynamic cerebral autoregulation usually measure the cerebral blood flow velocity (CBFV) response to changes in arterial blood pressure (ABP). We studied the effect of substituting ABP by cerebral perfusion pressure (CPP), expressed as the difference between ABP and intracranial pressure (ICP), in estimates of dynamic autoregulation obtained by transfer function analysis. CBFV, ABP and ICP were recorded during periods of physiological stability in 30 patients with severe head injury. Transfer function analysis was performed using the following combinations of input–output variables: ABP–CBFV, CPP–CBFV and CBFV–ICP. Frequency and time-domain (step response) functions were averaged for recordings with mean ICP = 20 mmHg (group B). The ABP–CBFV transfer function parameters and step response for group A were similar to previous studies in normal subjects, but group B showed deterioration of dynamic autoregulation. Radically different step responses were obtained from both groups for the CPP–CBFV transfer function and the coherence was not significantly improved. The CBFV–ICP transfer function had the highest values of coherence and indicates that changes in CBFV are the cause of spontaneous fluctuations in ICP. Furthermore, the ICP step response plateau was significantly higher for group B than for group A. An alternative calculation of the CBFV step response to changes in CPP resembled the corresponding responses for the ABP input. For spontaneous fluctuations in ABP, ICP and CBFV, it is not possible to calculate the CPP–CBFV transfer function directly due to the high positive correlation between ICP and CBFV, but an alternative estimate can be obtained by using the CBFV–ICP transfer function. The latter could also be useful as a method to assess intracranial compliance in head injury patients.

Comparative effects of calcipotriol solution (50 μg/ml) and betamethasone 17-valerate solution (1 mg/ml) in the treatment of scalp psoriasis

Abstract: The efficacy, tolerability and safety of calcipotriol solution and betamethasone 17-valerate solution were compared in a multicentre, prospective, randomized, double-blind, parallel group study. Four hundred and seventy-four patients with scalp psoriasis were recruited from si European countries and Canada. Following a 2-week without period, either calcipotriol solution (50 μg/ml) or betamethasone 17-valerate solution (1 mg/ml) was applied twice daily For 4 weeks. After this time, patients who required no further active treatment were observed for relapse. Retreatment with calcipotriol was offered to those patients who relapsed, and who were originally in the calcipotriol-treated group